Project Summary IgE-mediated peanut allergy is one of the most serious food allergies. There is no approved curative therapy for peanut allergy. Allergen specific immunotherapy (AIT) is the only disease-modifying treatment for peanut allergy, but the treatment can cause severe side effects. AIT based on natural allergen extracts or recombinant allergens is able to cross-link mast cell- or basophil-bound IgE/FcεR1complexes and contains allergen specific T-cell epitopes and thus can induce both immediate and late-phase side effects. A new approach, B-cell epitope based vaccine contains allergen-specific peptides, which do not have allergenic activity (ability to cross-link mast cell- or basophil- bond IgE/FCεR1complex) themselves and lack allergen-specific T cell epitopes and therefore, is safer than vaccines that are based on natural allergen extracts or recombinant allergens. In this study, we propose to design B-cell epitope based vaccines that contain carefully-selected, novel specific mimotopes . In Aim 1, we will design, express, purify and characterize mimotope-based fusion proteins. In Aim 2, we will perform vaccination with mimotope-based fusion proteins and test the efficacy of these mimotope-based vaccines in a well-established mouse model and a humanized mouse model of peanut allergy. The overall goal of this research is to design a new mimotope-based vaccine feasible for the treatment of existing peanut allergy.